trial of pamrevlumab (fg-3019), in non-ambulatory participants with duchenne muscular dystrophy (dmd)

Conditions: Duchenne Muscular Dystrophy

Summary: this is a phase 2, open-label, single arm trial of pamrevlumab (fg-3019) to estimate pamrevlumab's safety and efficacy in non-ambulatory participants with dmd.

the study will include a screening period, main study period, open-label extension (ole) period, and follow-up period 4 weeks after the last dose. all participants who complete the main portion of the study for a minimum of 104 weeks (2 years) will be rolled over to an ole for up to an additional 208 weeks (4 years).

Eligibility criteria:
inclusion criteria: * written consent/assent by participant and/or legal guardian as per regional and/or institutional review board (irb) requirements * non-ambulatory * brooke score for arms and shoulders ≤5 * diagnosis of dmd by medical history and confirmed duchenne mutation in available genetic testing using a validated genetic test * able to perform spirometry * able to undergo cardiac and extremity (upper arm) mri * percent predicted fvc between 40 and 90, inclusive * at least one historical ppfvc predicted value within 18 months of baseline * left ventricular ejection fraction ≥ 45% as determined by cardiac mri at screening or within 3 months prior to day 0 * participants currently receiving heart failure cardiac medications (for example, angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers) must achieve a stable regimen for at least 3 months prior to screening * on a stable dose of corticosteroids for a minimum of 6 months prior to screening with no substantial change in dosage for a minimum of 3 months (except for adjustments for changes in body weight) prior to screening and no foreseen change in corticosteroid use during the course of study participation * received pneumococcal vaccine and is receiving annual influenza vaccinations * adequate renal function: cystatin c ≤1.4 mg/liter (l) * adequate hematological function 1. platelets \>100,000/microliter (μl) 2. hemoglobin \>12 grams (g)/deciliter (dl) 3. absolute neutrophil count \>1500/μl * adequate hepatic function 1. no history or evidence of liver disease 2. gamma glutamyl transferase (ggt) ≤3 x upper limit of normal (uln) 3. total bilirubin ≤1.5 x uln * if sexually active, will use medically accepted contraceptives during participation in the study and for 3 months after the last dose of study drug exclusion criteria: * requires ≥16 hours continuous ventilation * prior or ongoing medical condition that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of 156 weeks of treatment and follow-up would be completed, or could impair the assessment of study results * anticipated spine surgery within 156 weeks * severe uncontrolled heart disease, including any of the following: 1. need for intravenous diuretics or inotropic support within 3 months prior to screening 2. hospitalization for a heart failure exacerbation or arrhythmia in last 3 months * arrhythmia requiring anti-arrhythmic therapy * hospitalization due to respiratory failure in the last 6 weeks * poorly controlled asthma or underlying lung disease such as bronchopulmonary dysplasia * known or suspected active hepatitis b or c or history of human immunodeficiency virus (hiv) * body mass index (bmi) ≥40 kilograms (kg)/square meter (m\^2) or weight \>117 kg * exposure to another investigational drug or another approved product for dmd (for example, eteplirsen or golodirsen) within 28 days prior to start of study treatment * exposure to another investigational drug or another approved product for dmd (e.g. eteplirsen) within 28 days prior to start of study treatment (or 5 half-lives of the product whichever is longer) prior to first screening visit with the exception of deflazacort. use of deflazacort, if regarded by the principal investigator as standard of care, is allowed.

Keywords: duchenne muscular dystrophy dmd non-ambulatory